The objective of this proposal is to gain knowledge about the organization of visceral sensory processing in the upper cervical spinal cord. Recent observations led to the concept that this region may integrate visceral information to modulate nociceptive responses. Preliminary evidence in rats suggests that upper cervical neurons with descending projections process noxious inputs to produce inhibitory effects on sensory transmission in lower segments. Additionally a group of descending neurons in C1-C2 segments have respiration-phased discharge. No clear contribution to normal breathing has been found for these neurons. A possible function that has not been considered previously is that visceral input to high cervical respiratory neurons may influence the descending outflow to produce the sensation of dyspnea. The overall hypothesis is that upper cervical neurons with descending projections are excited by visceral spinal input and vagal input, and thus could modulate neuronal activity in lower spinal segments. Specific aims are designed to answer the following questions: 1) What is the anatomical distribution and neurochemical content of upper cervical propriospinal neurons? 2) Does chemical activation/inactivation of upper cervical neurons affect spinoparabrachial or spinothalamic tract neurons in thoracic and lumbosacral segments? 3) Are C1-C2 descending propriospinal neurons, including respiratory neurons, excited by visceral afferent inputs? 4) What are the electrophysiologic, morphologic and neurochemical characteristics of single C1-C2 neurons examined after intracellular penetration? Neuroanatomical, immunohistochemical and neurophysiological techniques will be used to determine basic information about upper cervical propriospinal neurons, including respiratory neurons. Data derived from these studies will provide understanding of central neural mechanisms which may be involved in conditions such as autonomic dysreflexia, silent myocardial ischemia, and dyspnea.